The overall goal for this proposal is to develop a unified, asymmetric approach to the akuammiline alkaloids, a diverse class of indoline-containing natural products. These natural products have a range of biological activities and may serve as leads for the development of new therapeutics to treat cancer, pain, inflammation, diabetes, and depression. In addition to their promising bioactivities, these compounds also possess highly complex structures. A streamlined synthetic route will provide access to a variety of these structures in an efficient manner, while addressing several challenges prevalent in chemical synthesis. In addition, with this research, useful quantities of these compounds will be accessible for biological testing. The goals of this proposal will be accomplished through three main phases. First, a synthetic route to picrinine, one of the natural products of this family, will be developed. This synthesis wll help us develop the chemistry needed to access the akuammiline natural products, while also providing access to a family member that has never been synthesized before. Next, an asymmetric route to an early-stage intermediate will developed, which will potentially provide access to (-)-picrinine, (-)-aspidophylline A, and other natural products in an enantiospecific fashion. Other targets that will be prepared, none of which have been synthesized before, are: (+)-strictamine, (-)-11-methoxyvincorine, (-)-11-demethoxyquaternine, and (-)-?-akuammigine. It should be stressed that each of these compounds contains a different core structure. As such, establishing a generalized route to include these compounds will advance the field of chemical synthesis due to the structural diversity that the route promises to build. In addition, any compounds that come from this proposed research will be submitted for biological evaluation. This opens the possibility of conducting further research to fully gauge the biological activities f these compounds with respect to their structures and targets.